The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins.
The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins.
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发表时间：
1999-11
影响因子：
1.2
通讯作者：
T. Tseng;Kevin Gratwick;J. Kollman;Daniel Park;D. Nies;A. Goffeau;M. Saier
中科院分区：
文献类型：
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作者：
T. Tseng;Kevin Gratwick;J. Kollman;Daniel Park;D. Nies;A. Goffeau;M. Saier
以前的一份报告确认并归类了一个革兰氏阴性细菌药物和重金属渗出的小家族，现在通常被称为RND家族(TC No.2)。我们在这里表明，这个家庭实际上是一个无处不在的超级家庭，在所有主要王国都有代表性。我们报告的系统发育分析将RND超家族中的七个家族定义为：(1)重金属外排(HME)家族(革兰氏阴性细菌)，(2)疏水/两亲性外排-1(HAE1)家族(革兰氏阴性细菌)，(3)结瘤因子输出蛋白(NFE)家族(革兰氏阴性细菌)，(4)SecDF蛋白分泌辅助蛋白(SecDF)家族(革兰氏阴性和革兰氏阳性细菌)，(5)疏水/两亲性外排-2(HAE2)家族(革兰氏阳性细菌)，(6)真核类固醇稳态(ESH)家族；(7)疏水/两亲性外排-3(HAE3)家族(古生菌和螺旋体)。功能未知的蛋白质被鉴定为RND超家族的成员，但不属于这七个家族。一些真核同系物的功能是酶和受体，而不是(或除了)转运蛋白。所有七个家族的成员的大小和拓扑模式都显示出惊人的相似，统计分析建立了共同的血统。每个家族内的蛋白质的多重比对允许衍生出家族特有的特征序列。对已报道结果的结构、功能、机制和进化意义进行了讨论。
A previous report identified and classified a small family of gram-negative bacterial drug and heavy metal efflux permeases, now commonly referred to as the RND family (TC no. 2.6). We here show that this family is actually a ubiquitous superfamily with representation in all major kingdoms. We report phylogenetic analyses that define seven families within the RND superfamily as follows: (1) the heavy metal efflux (HME) family (gram negative bacteria), (2) the hydrophobe/amphiphile efflux-1 (HAE1) family (gram negative bacteria), (3) the nodulation factor exporter (NFE) family (gram negative bacteria), (4) the SecDF protein-secretion accessory protein (SecDF) family (gram negative and gram positive bacteria as well as archaea), (5) the hydrophobe/amphiphile efflux-2 (HAE2) family (gram positive bacteria), (6) the eukaryotic sterol homeostasis (ESH) family, and (7) the hydrophobe/amphiphile efflux-3 (HAE3) family (archaea and spirochetes). Functionally uncharacterized proteins were identified that are members of the RND superfamily but fall outside of these seven families. Some of the eukaryotic homologues function as enzymes and receptors instead of (or in addition to) transporters. The sizes and topological patterns exhibited by members of all seven families are shown to be strikingly similar, and statistical analyses establish common descent. Multiple alignments of proteins within each family allow derivation of family-specific signature sequences. Structural, functional, mechanistic and evolutionary implication of the reported results are discussed.